How to interpret stroke-like attacks in the context of mitochondrial disease

How to interpret stroke-like attacks in the context of mitochondrial disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review How to interpret stroke-like attacks in the context of mitochondrial disease Dr Gülhan Karakaya Molla, Prof. Dr Özlem Ünal Uzun, Dr Khanim Baba Zada, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6950590/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction : Stroke-like attacks are defined as events characterized by the sudden onset of neurological symptoms with clinical manifestations similar to those of a stroke. However, they are distinguished by the presence of radiological lesions that are incompatible with the vascular territory. MELAS syndrome, which is characterized by metabolic encephalopathy, lactic acidosis, and stroke-like attacks, has been identified as the first genetically defined and most widely known mitochondrial cause of stroke-like attacks. It has been demonstrated that stroke-like attacks may occur in the course of a variety of mitochondrial diseases, including those that are the result of nuclear DNA mutations. Objective : In this retrospective, multicenter, observational cohort study, we sought to determine the clinical, radiological, EEG, and genetic characteristics of patients with mitochondrial gene mutations presenting with stroke-like attacks and the frequency and treatment of stroke-like attacks. Methods : Thirty-six patients with mitochondrial disease with stroke-like episodes, all diagnosed by molecular analysis from nine pediatric metabolic disease centers in the Marmara Region of Turkey, were included in the study. Demographic characteristics, symptoms, clinical features, cranial MRI, EEG findings, and genetic characteristics were evaluated. Conclusion : The present study demonstrated that stroke-like attacks in genetically diagnosed mitochondrial diseases are most commonly observed in MELAS and POLG mutations. However, they may also develop in rare subtypes such as CoQ10 deficiency, beta-ketothiolase deficiency ( ACAT1 mutation), and Leigh syndrome. During attacks, cranial MRI showed bilateral cortical lesions incompatible with vascular distribution, often located frontotemporally, and EEG shows focal epileptiform activity. In MELAS, clinical improvement was observed withiv L-arginine treatment initiated in the acute period, and it was determined that long-tMEerm oral arginine may be effective in reducing the frequency of attacks. The findings emphasize that stroke-like episodes should be considered in the differential diagnosis of mitochondrial diseases in the presence of sudden onset neurological findings. Stroke-like episodes mitochondrial diseases. MELAS POLG mutations CoQ10 deficiency Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Stroke is an important neurologic emergency that may lead to serious morbidity and mortality, although it is observed more rarely in childhood than in adults. The World Health Organization defines stroke as "a rapidly developing set of clinical findings due to focal or global impairment of cerebral functions, lasting longer than 24 hours or resulting in death" ( 1 ). While the etiologies of stroke in the pediatric population spread over a wide spectrum, hereditary metabolic diseases are among the rarer causes. Nevertheless, they have special importance in terms of the need for early diagnosis and specific treatment ( 2 , 3 ). Stroke-like attacks are characterized by acute or subacute onset neurologic findings incompatible with a classical vascular anatomical distribution ( 4 ). The best-defined example in the mitochondrial disease group with stroke-like attacks is MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome ( 5 ). In addition, Kearns-Sayre syndrome, Leigh syndrome, MERRF, LHON (Leber's hereditary optic neuropathy), and non-syndromic mitochondrial diseases, especially POLG mutations, have also been associated with similar clinical pictures ( 6 , 7 ). The clinical spectrum is quite broad. While migraine-like headaches and epileptic seizures are frequently seen before the attack, various symptoms, including altered consciousness, hemiparesis, aphasia, cortical visual loss, and neuropsychiatric findings, may occur in the acute phase of the attack ( 7 , 8 ). On imaging, lesions are frequently localized in occipital, parietal, or posterior temporal lobes, limited to the cortex, asymmetric, and incompatible with vascular distribution ( 4 , 9 ). Electroencephalography (EEG) findings contribute to the diagnosis of encephalopathic changes and focal epileptiform activity ( 10 ). Treatment aims to reduce metabolic stress, ensure seizure control, and avoid agents with the potential for mitochondrial toxicity. L-arginine treatment administered in the acute period has been reported to provide symptomatic improvement in some patients ( 11 , 12 ). In this study, we retrospectively evaluated the clinical, laboratory, imaging, and EEG characteristics of stroke-like episodes in children with molecularly confirmed mitochondrial disease who were followed up in nine different pediatric metabolic centers across Turkey. Methods The retrospective medical records of 36 patients who were followed up in the pediatric metabolism and nutrition divisions of nine centers in the Marmara Region in Turkey were analyzed. Current age, age at first attack and age at diagnosis, clinical features, growth parameters, laboratory, radiological, EEG and molecular analysis findings were recorded. The data obtained in the study were analyzed using SPSS 23 (Statistical Package for Social Sciences) software. In statistical analyses, Chi-square analysis and Fisher Exact test were used to examine the relationships between categorical variables. Kruskal-Wallis test and Mann-Whitney U test were used to evaluate the differences between continuous variables since parametric test assumptions were not met. In all analyses, the significance level was determined as p < 0.05 and the confidence level was evaluated as 95%. The ethics committee approval of the study was given by the “Tekirdağ Dr. İsmail Fehmi Cumalıoğlu City Hospital Clinical Research Ethics Committee” on 28.08.2024 with the number 119. Findings Demographic Characteristics: Among the 36 patients with a genetic diagnosis of mitochondrial diseases, 52.8% (n = 19) were female and 47.2% (n = 17) were male. Regarding age distribution, the highest proportion was observed in the 5.01–10-year age group at 25% (n = 9), whereas the lowest proportion was in the 10.01–15-year age group at 13.9% (n = 5). The most common period for the onset of initial symptoms was under 5 years of age, accounting for 58.3% (n = 21), while the lowest frequency was recorded in the 15.01–20-year age group at 2.8% (n = 1). In terms of age at diagnosis, 41.7% (n = 15) of the patients were diagnosed before the age of 5 years, whereas 13.9% (n = 5) were diagnosed after the age of 20 years (Table 1, table 8). Genetic Diagnoses and Distribution by Diagnosis : Of the 36 patients with a genetic diagnosis of mitochondrial diseases, 41.7% (n=15) were diagnosed with MELAS, 25% (n=9) with Coenzyme Q10 deficiency, 11.1% (n=4) with Leigh syndrome and 8.3% (n=3) with POLG mutation. There were also cases with FBXL mutation 5.5% (n=2), LHON 2.8% (n=1), Triple H syndrome 2.8% (n=1), and ACAT1 (n=1) 2.8% deficiency (Graph 1). Stroke-like Attacks: Of the 14 patients with stroke-like attacks, 42.8% (n=6) were diagnosed with MELAS and 21.4% (n=3) with POLG. These episodes were also observed in individuals diagnosed with Coenzyme Q10 deficiency 14.2% (n=2), Leigh syndrome 14.2% (n=2), and ACAT1 deficiency 7.1% (n=1) (Figure 1). A comparative analysis of the data reveals that the most prevalent age group experiencing stoke-like attacks was 5.01-10 years (42.9%), followed by 15.01-20 years (28.6%). The highest proportion of individuals without an attack was in the age group above 20 years, with 27.3%. However, no statistically significant relationship was found between age groups and stroke-like attacks (χ² = 7.955; p = 0.078) (Table 4). Clinical Findings Associated with Stroke Attacks : The prevalence of seizures was found to be significantly higher in patients with a stroke-like episode compared to those without such an episode (64.3% vs. 22.7%, p < 0.05) (p=0.013). Similarly, hemiparesis was observed in 35.7% of patients with a history of attack compared to only 4.8% in those without a history of attack (p=0.028). Psychiatric disorders were also associated with stroke-like attacks; being present in 44.4% of those who had an attack and 9.5% of those who did not (p=0.049). Ophthalmoplegia and hemianopsia were reported only in individuals who had an attack, and both findings were statistically significant (p=0.048) (Graph 2). When genetic subtypes were analyzed, migraine headache was reported 100% in FBXL4 mutations, ACAT1 deficiency, and Triple H patients, 88.9% in Coenzyme Q10 deficiency, 75% in Leigh syndrome, and 40% in MELAS. Cognitive decline was present in all patients (100%) with Leigh, FBXL4 mutations and LHON. Decreased muscle mass was significantly observed in patients with MELAS, FBXL4 , and Triple H. Cataracts were detected in 50% of individuals with POLG mutation only, which was distinctive in this respect. Hearing loss was observed in 50% of patients with FBXL4 mutation (Graph 3). An evaluation of body mass index (BMI) revealed mean BMI values of 16.49±3.85 in patients with MELAS, 23.83±11.47 in patients with CoQ10 deficiency, 11.98±2.97 in Leigh syndrome, and 27.34±15.37 in the FBXL, LHON, Triple H, ACAT1 group. Although no significant difference was found between the diagnosis groups (χ² = 7.371; p = 0.061), the p-value is close to the significance limit and suggests that there may be BMI trends according to diagnosis (Graph 4). Seizures and EEG findings : A history of seizures was identified in 64.3% of stroke patients, while 35.7% had no history of seizures. In the evaluation of seizure types, 35.7% of patients experienced generalized seizures and 28.6% experienced focal seizures. Analysis of EEG findings revealed that EEG evaluation was not performed in 21.4% of the patients, whereas focal epileptiform activity was detected in 35.7%. Additionally, generalized epileptiform activity was observed in 21.4% of patients, while 42.9% showed no evidence of generalized epileptiform activity (Table 3). Magnetic Resonance Imaging (MRI) Findings : Cranial MRI revealed lesions in 51.6% (n=16) of the patients. Of the lesions, 73.3% affected both hemispheres, 20% affected the left hemisphere, and 6.7% affected the right hemisphere. Lesions were most frequently observed in the frontal and temporal lobes (33.3%; n=4), with lower rates in the parietal lobe (24%; n=3) and occipital lobe (8.4%; n=1). Regarding lesion resolution, disappearance occurred within 2–6 months in 37.5% (n = 3) of patients, between 6 months and 1 year in 12.5% (n = 1), and after more than 1 year in 50% (n = 4) of the patients with available data (Table 2). MR Spectroscopy Findings : MR spectroscopy was not performed in 52.1% (n=18) of the patients; no lactate peak was found in 25.8% (n=8) and 16.1% (n=5) of the patients who underwent MR spectroscopy (Table 2). Laboratory Findings : The mean plasma lactic acid level was 22.61±23.24 mg/dL in individuals who had a stroke-like attack, while this value was 10.21±12.39 mg/dL in those who did not have an attack. The difference between the two groups was not statistically significant (z=-1.785; p=0.078), but it was close to the significance threshold (Figure 5). Table 1: Distribution of demographic information and variables related to diagnosis in patients with mitochondrial diseases experiencing stroke-like attacks Variable Category n % Gender Male 17 47,2 Female 19 52,8 Age (year) <5 7 19,4 5.01-10 9 25,0 10.01-15 5 13,9 15.01-20 8 22,2 Over 20 7 19,4 Age at onset of first symptoms (year) < 5 21 58,3 5.01-15 6 16,7 10.01-15 4 11,1 15.01-20 1 2,8 Over 20 4 11,1 Age at diagnosis (year) <5 15 41,7 5.01-10 5 13,9 10.01-15 9 25,0 15.01-20 2 5,6 Over 2 5 13,9 Duration of follow-up (year) 4 8 22,2 Diagnosis MELAS 15 41,7 Coenzyme Q10 deficiency 9 25,0 Leigh syndrome 4 11,1 POLG 3 8,3 FBXL 2 5,5 LHON 1 2,8 Triple H syndrome 1 2,8 ACAT1 deficiency 1 2,8 MELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, LHON: Leber's hereditary optic neuropathy. Table 2: Cranial MR findings of the patients n % Cranial MRI Lesion 16 51,6 No lesion 15 48,4 Localization Lesions 1 Right hemisphere 1 6,7 Left hemisphere 3 20 Bilateral hemispheres 11 73,3 Localization Lesions 2 Frontal 4 33,3 Temporal 4 33,3 Parietal 3 25 Occipital 1 8,4 Time to Resolution of Lesions (Month) 2-6 3 37,5 6-12 1 12,5 >12 4 50 MR Spectroscopy Not performed 18 58,1 Lactate peak detected 5 16,1 No lactate peak 8 25,8 n: frequency, %: percentage Table 3: Distribution of stroke patients (n=14) regarding diagnosis and seizures n % Seizure Yes 9 64,3 No 5 35,7 Seizure Type Focal seizure 4 28,6 Generalized seizure 5 35,7 No information 5 35,7 EEG Finding 1 No EEG 4 28,5 Focal epileptiform activity 5 35,7 No focal epileptiform activity 5 35,7 EEG Finding 2 Generalized epileptiform activity 3 21,4 No generalized epileptiform activity 6 42,9 No EEG 5 35,7 EEG Finding 3 Epileptiform activity in the left frontotemporal region 2 50 Epileptiform activity in the temporaparietal region 1 25 Epileptiform activity in the left hemisphere 1 25 Table 4: Age and stroke attack findings Stroke-like Attacks Total χ² p Yes No Age (years) 20 n 1 6 7 % 7,1% 27,3% 19,4% Total n 14 22 36 % 100,0% 100,0% 100,0% The graph shows the incidence of stroke-like attacks in individuals with different diagnostic groups. It is noteworthy that stroke-like attacks are more common in individuals with MELAS and POLG mutations. There is one patient diagnosed with ACAT1 and had a stroke attack. In the graph, the red line indicates the significance limit (p=0.05). The heat map above shows the percentages of certain neurological and systemic symptoms by diagnosis. The color intensity is darker the more common the symptom is in that diagnostic group The graph shows the mean and standard deviation of body mass index (BMI) of individuals belonging to different diagnostic groups. The 'mean ± standard deviation' values for each diagnostic group are also indicated on the graph. The graph shows the mean and standard deviation values of lactic acid levels in individuals with and without stroke-like episodes. Lactic acid levels were higher and the distribution was wider in individuals with stroke. This difference was statistically borderline significant (p=0.078). Table 8 : Clinical findings of the patients Patient No Gender Age (years) Diagnosis Mutation Age at onset of first symptoms (months) Age at diagnosis (months) Number of stroke-like episodes Localization of lesions on cranial MRI EEG findings Lactate levels mmol/L (last viewed) Duration of oral L-Arginine use 1 Female 40 MELAS MT-TK -M8362T 444 480 No lesion 21 2 months 2 Female 28 MELAS TRLN1 -A3243G 300 324 No lesion Frontal deceleration 2,5 22 days 3 Male 16,9 MELAS TRLN1 -A323G 18 60 Frontal 34 3 months 4 Male 9 MELAS MT-TK -M3290T>C 12 12 2 Parietal Epileptiform activity in the left fronto-temporal region 40 5 Female 50 MELAS TRLN1 -A3243G 444 564 Frontal 22 days 6 Male 2 MELAS MT-TW - 5543T>C 34 36 No lesion 3,2 7 Male 11,1 MELAS MT-TK -M8362T 84 132 No lesion 44 3 months 8 Male 40 MELAS TRLN1 -Nt3243 432 468 4 Parietal Epileptiform activity in the left fronto-temporal region 7,4 9 Female 5 MELAS MT-TW- 5543T>C 12 12 No lesion 4 10 Female 3,7 MELAS TRLN1 -m3243A>G 5 36 No lesion Temporo parietal bilateral epileptiform activity 9 days 11 Male 9 MELAS MT-TL1 m3271T>C 88 96 2 Occipital Low background activity and rare spike-like waves in the right parieto-occipital 11 days 12 Female 15,3 MELAS TRLN1 -A3243G 84 156 2 No lesion Left hemisphere epileptiform activity 7 40 days 13 Male 5,8 MELAS TRLN1 -A323G 6 36 1 Temporal 67 11 months 14 Male 18,9 MELAS TRLN1 -A323G 144 144 Frontal 3,9 15 Male 18 MELAS MT-TL1 m3271T>C 156 180 5 Parietal 60 34 days 16 Female 21,8 Coenzyme Q10 Deficiency COQ8A c.911C>T hom 204 216 No lesion Disorganization in the left fronto-temporal region 3,1 17 Male 4,5 Coenzyme Q10 Deficiency COQ4 c.437T>G 2,5 12 2 Temporal 5,9 18 Female 17,8 Coenzyme Q10 Deficiency COQ8 c.811C>T (p.ARG) 18 180 No lesion Multifocal generalized epileptiform anomaly 1,4 19 Female 19,1 Coenzyme Q10 Deficiency COQ8A c.914A>T hom 20 30 1 Frontal 3,6 1day 20 Male 22,9 Coenzyme Q10 Deficiency COQ8B hom. c1199dup 96 252 No lesion 5,5 21 Male 13 Coenzyme Q10 Deficiency COQ8A c.811 C>T (p.ARG) 48 144 No lesion Multifocal generalized epileptiform anomaly 7 22 Female 6,6 Coenzyme Q10 Deficiency COQ8A c.1344_1345dup hom. 48 60 No lesion 1,49 23 Male 6,00 Coenzyme Q10 Deficiency COQ4 c.437T>G (p.Phe146C) 48 48 No lesion 3,50 24 Female 10,9 Coenzyme Q10 Deficiency COQ8 c.811C>T 9(p.ARG) 18 72 No lesion 3,40 25 Female 2,5 Leigh LINS gen c.554a>G 12 12 Temporal 20 26 Female 1,9 Leigh SURF1 c.530T>G hom 12 12 3 No lesion 2,2 3 days 27 Male 6,9 Leigh MT-ND5 M.13513G>A 42 48 No lesion 28 Female 18 Leigh SURF1 gene c54+5G>T (IVS1+5G>T) hom 60 216 1 No lesion 28 29 Female 1,4 POLG c.3286C>T p.Arg1096h 12 15 1 No lesion Bilateral central disorganization in sleep 30 Male 7,3 POLG c.1760C>T P. Pro587leu */c1760C>T.pro587leu 72 80 1 No lesion 36 31 Female 9,1 POLG c.911T>G (p. Leu304Arg) hom 96 102 1 No lesion 12 32 Female 12,5 FBXL4 FBXL4 c.445G>A 1 11 No lesion 7,6 33 Male 11 FBXL4 FBXL4 c.445G>A 2 9 No lesion 10,2 34 Male 18,5 LHON LHON 11778G>A 156 156 No lesion 1,5 35 Female 30 Triple-H syndrome SLC25A15 hom 132 156 Temporal 23 120 months 36 Female 5,5 ACAT1 ACAT1 c.301C>T hom 24 2 No lesion 2,2 Discussion In this multicenter observational cohort study, the clinical, radiological, EEG, and genetic features of genetically diagnosed mitochondrial diseases, the frequency of stroke-like episodes, associated findings, and treatment approaches were evaluated. Although the data obtained were generally consistent with the existing literature, they also showed some remarkable differences. Stroke-like attacks were most frequently observed in individuals diagnosed with MELAS (42.9%), as reported in the literature ( 11 ). In the majority of these patients (66.6%), m.3243A > G mutation was found in the MT-TL1 gene, and this rate was consistent with previously reported data ( 13 ). POLG mutation stood out as the second most common cause of stroke-like attacks, and this was consistent with the frequency ranking in the literature ( 14 ). Coenzyme Q10 (CoQ10) deficiency is one of the rare mitochondrial disorders that develop due to mutations in genes involved in ubiquinone synthesis. In the literature, there are a limited number of cases and small patient series in which stroke-like attacks have been reported to be associated with mutations in biosynthesis genes such as COQ8A (ADCK3) and COQ4 ( 15 , 16 ). In our study, stroke-like attacks were observed in two of nine patients diagnosed with CoQ10 deficiency. This finding indicates that CoQ10 deficiency may rarely lead to stroke-like attacks and emphasizes that neurologic symptoms should be carefully evaluated in this patient group. In beta-ketothiolase deficiency due to ACAT1 mutation, basal ganglia involvement, and neurologic findings may be observed during ketoacidosis attacks that develop after metabolic stress. In the literature, a case of stroke-like episode with ketoacidosis after infection has been reported (17). In our study, a stroke-like episode was observed during the metabolic crisis in a patient with ACAT1 mutation. This finding demonstrates that ACAT1 -related metabolic diseases may present not only with metabolic crises but also with acute neurologic complications. It is therefore suggested that stroke-like episodes should definitely be considered in the differential diagnosis in this patient group. Stroke-like episodes associated with Leigh syndrome have rarely been described in the literature. In a case report, a three-month-old female infant with post-infectious encephalopathic features and neurologic symptoms, including hypotonia, apnea, and optic atrophy was diagnosed with Leigh syndrome. This case suggests that metabolic stress may trigger neurologic findings in Leigh syndrome, and the disease may present with stroke-like episodes ( 18 ). In our series, it was observed that two of the four patients with Leigh syndrome developed stroke-like episodes in relation to metabolic stress. This observation reveals that Leigh syndrome may present not only as a progressive neurodegenerative disorder but also with acute neurologic decompensations triggered by metabolic stress. It emphasizes the necessity for early diagnosis, close follow-up, and prevention of metabolic crises in this patient group. In a study conducted by Chloe Durrleman et al. on 120 pediatric patients, it was reported that the first symptoms of the patients started between 0–28 months, and the first stroke-like attacks occurred between 17–124 months. In addition, it was reported that 32% of the patients had their first stroke-like attack over the age of 35 years in this series ( 19 ). In our study, it was observed that the first symptoms usually started before the age of 5 years, and the first stroke-like attacks occurred mostly in the age range of 5.01-10 years (42.9%). The youngest patient was 1.9 years old, and the oldest patient was 40 years old. This shows that the development of attacks is not limited by age and can occur at any age. Gender distribution was equal (F/M: 7/7), and gender was not a determining factor in attacks. In this respect, it differs from some studies in the literature ( 19 ). An analysis of the clinical symptoms revealed that headache was the most prevalent indication associated with stroke-like attacks. This was followed by decreased muscle mass, myopathy, and seizures. In a study by Chaolong Xu et al. involving children with MELAS syndrome, muscle weakness was defined as an indicator of severe mitochondrial dysfunction ( 20 ). The high seizure frequency found in our study and its significant association with stroke-like episodes support the hypothesis that these episodes may be triggered by epileptic seizures ( 20 , 19 ). In a study conducted by Yi Shiau Ng et al. on MELAS patients, it was reported that 91% of the patients had symptoms indicating mitochondrial dysfunction before the stroke-like attack, and the most common symptom was sensorineural hearing loss ( 21 ). In our series, findings such as hearing loss, hemianopsia, cortical blindness, recurrent vomiting, and myopathy were frequently observed before stroke-like attacks in individuals diagnosed with MELAS. In addition, sensorineural hearing loss was one of the most common symptoms in these patients. Although no statistical significance was found between stroke-like attacks and some demographic variables such as age, gender, and BMI, low BMI in MELAS and Leigh patients is remarkable. This indicates that short stature and nutritional deficiency also accompany these patients and is in parallel with the literature ( 21 ) Studies have shown that brain lactate levels increase with disease progression in MELAS patients, and this increase reflects a progressive shift in oxidative redox potential. These findings suggest that lactate levels may be an important biomarker for monitoring the course of the disease and establishing a diagnosis. In our study, mean lactate levels were found to be significantly higher in patients with a stroke-like attack compared to those without an attack ( 22 ). This difference was close to the statistical significance limit and may support the potential role of lactic acidosis in the pathogenesis of the attack. Therefore, regular monitoring of lactate levels may be useful in clinical follow-up. In radiologic evaluations, Durrleman et al. reported that bilateral cortical diffusion hyperintensity and hyperperfusion were prominent in cranial MR images obtained in the first 48 hours, and this condition developed due to energy metabolism disorders different from classical ischemic strokes ( 21 ). In our study, bilateral lesions were observed in all seven patients imaged in the acute period, and the most common site of involvement was frontotemporal lobes. When EEG findings were analyzed, focal epileptiform activity was found to be more frequent in accordance with the literature ( 14 ). With regard to the treatment approaches that were employed, a retrospective analysis by Ganetzky et al. reported that clinical improvement was achieved in 47% of patients who received intravenous (iv) arginine treatment. A better response to treatment was observed, especially in cases of hemiplegic attacks ( 23 ). In our series, all patients with stroke-like attacks received iv arginine treatment in the acute phase of the attack, and clinical improvement was observed, especially in the early onset case in Durrleman's study, recurrent attacks were reported in three patients in an 8-year follow-up, whereas recurrent stroke-like attacks were observed in six patients in our series, with five attacks in one MELAS patient and four attacks in another ( 19 ). In systematic reviews on the efficacy of oral L-arginine treatment, it was emphasized that the clinical benefit of acute or prophylactic use was limited, but methodological deficiencies were found in these studies ( 24 ). On the other hand, some studies have suggested that oral L-arginine may reduce the frequency and severity of stroke-like episodes. In a study including six MELAS patients, it was reported that oral L-arginine treatment at a dose of 0.15–0.3 g/kg/day administered for 18 months resulted in significant improvement ( 25 ). In our study, long-term oral L-arginine treatment was administered to 10 MELAS patients with recurrent stroke-like attacks, and significant improvement was observed in the clinical course. In addition, Chaolong Xu et al. reported that 56% of patients receiving L-arginine and antiepileptic treatment showed significant clinical improvement ( 20 ). Conclusion This study showed that stroke-like attacks in genetically diagnosed mitochondrial diseases are most commonly observed in MELAS and POLG mutations. However, they may also develop in rare subtypes such as CoQ10 deficiency, ACAT1 mutation, and Leigh syndrome. During attacks, the presence of bilateral cortical lesions on cranial MRI—often located in the frontotemporal regions and inconsistent with vascular distribution—and the detection of focal epileptiform activity on EEG were diagnostically significant findings. Clinical improvement was observed with iv L-arginine treatment initiated in the acute period, and it was determined that long-term oral arginine may be effective in reducing the frequency of attacks. The findings emphasize that stroke-like episodes should be considered in the differential diagnosis of mitochondrial diseases in cases of sudden onset neurological findings. Declarations Acknowledgments : This research received no external funding. Author contributions: All authors contributed to the study conception and design . All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Competing interests: Authors state no conflict of interest. Informed consent : Informed consent was obtained from all individuals included in this study. References Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov at all. Cerebrovascular disease in the community: Results of a who collaborative study. Bull World Health Organ 1980; 58: 113-130. 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Ganetzky RD, Falk MJ. 8-year retrospective analysis of intravenous arginine therapy for acute metabolic strokes in pediatric mitochondrial disease. Mol Genet Metab. 2018 Mar;123(3):301-308. doi: 10.1016/j.ymgme.2018.01.010. Stefanetti RJ, Ng YS, Errington L, Blain AP, McFarland R, at all. l-Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes: A Systematic Review. Neurology. 2022 Jun 7;98(23):e2318-e2328. doi: 10.1212/WNL.0000000000200299. Almannai M, El-Hattab AW. Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline. Front Mol Neurosci. 2021 Aug 5;14:682780. doi: 10.3389/fnmol.2021.682780. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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University Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Dr Bülent","lastName":"Kara","suffix":""},{"id":474984955,"identity":"2bec565a-3104-43b6-befb-7454b60fb556","order_by":17,"name":"Prof. Dr Gülden Fatma Gökçay","email":"","orcid":"","institution":"Istanbul University Istanbul Faculty of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Prof.","middleName":"Dr Gülden Fatma","lastName":"Gökçay","suffix":""}],"badges":[],"createdAt":"2025-06-22 16:23:03","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6950590/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6950590/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85370505,"identity":"61f8c54f-ac94-4a5b-8574-7f0cdd1414d7","added_by":"auto","created_at":"2025-06-25 07:25:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103591,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 1: \u003c/strong\u003eFindings of stroke-like attacks at diagnosis\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/4e652416448d1bd93279ae03.png"},{"id":85370503,"identity":"a49aaeb1-ce6b-4c0a-b0a3-55bb92bc663e","added_by":"auto","created_at":"2025-06-25 07:25:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":129694,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 2: \u003c/strong\u003eDistribution of stroke attacks and symptoms.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/ab92b1834b151a95fbbb3b44.png"},{"id":85370515,"identity":"581ac80e-2d75-4abe-aaf9-4254a79d6aa6","added_by":"auto","created_at":"2025-06-25 07:25:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":125781,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 3: \u003c/strong\u003ePercentage of symptoms according to mitochondrial diseases\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/162df1004c9c960c5db86e03.png"},{"id":85370480,"identity":"c1d92f63-979a-48ae-9532-0f48b681a670","added_by":"auto","created_at":"2025-06-25 07:25:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":77724,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 4: \u003c/strong\u003eDiagnosis groups by BMI\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/b699dcf4abc909d7d57c8883.png"},{"id":85370523,"identity":"0533cec7-dc67-4942-bb09-9576f6e05e74","added_by":"auto","created_at":"2025-06-25 07:25:19","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":61575,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eGraph 5: \u003c/strong\u003eStroke attacks and lactic acid level findings\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/ddd52d256923c2a5c3178571.png"},{"id":85605744,"identity":"9c550f55-8baa-4289-99c7-8e14d01f9a84","added_by":"auto","created_at":"2025-06-29 06:38:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1672315,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6950590/v1/0b4cb954-ecb3-4518-af02-c99a8f212e4a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"How to interpret stroke-like attacks in the context of mitochondrial disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStroke is an important neurologic emergency that may lead to serious morbidity and mortality, although it is observed more rarely in childhood than in adults. The World Health Organization defines stroke as \"a rapidly developing set of clinical findings due to focal or global impairment of cerebral functions, lasting longer than 24 hours or resulting in death\" (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). While the etiologies of stroke in the pediatric population spread over a wide spectrum, hereditary metabolic diseases are among the rarer causes. Nevertheless, they have special importance in terms of the need for early diagnosis and specific treatment (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Stroke-like attacks are characterized by acute or subacute onset neurologic findings incompatible with a classical vascular anatomical distribution (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The best-defined example in the mitochondrial disease group with stroke-like attacks is MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In addition, Kearns-Sayre syndrome, Leigh syndrome, MERRF, LHON (Leber's hereditary optic neuropathy), and non-syndromic mitochondrial diseases, especially \u003cem\u003ePOLG\u003c/em\u003e mutations, have also been associated with similar clinical pictures (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The clinical spectrum is quite broad. While migraine-like headaches and epileptic seizures are frequently seen before the attack, various symptoms, including altered consciousness, hemiparesis, aphasia, cortical visual loss, and neuropsychiatric findings, may occur in the acute phase of the attack (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). On imaging, lesions are frequently localized in occipital, parietal, or posterior temporal lobes, limited to the cortex, asymmetric, and incompatible with vascular distribution (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Electroencephalography (EEG) findings contribute to the diagnosis of encephalopathic changes and focal epileptiform activity (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Treatment aims to reduce metabolic stress, ensure seizure control, and avoid agents with the potential for mitochondrial toxicity. L-arginine treatment administered in the acute period has been reported to provide symptomatic improvement in some patients (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, we retrospectively evaluated the clinical, laboratory, imaging, and EEG characteristics of stroke-like episodes in children with molecularly confirmed mitochondrial disease who were followed up in nine different pediatric metabolic centers across Turkey.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e The retrospective medical records of 36 patients who were followed up in the pediatric metabolism and nutrition divisions of nine centers in the Marmara Region in Turkey were analyzed. Current age, age at first attack and age at diagnosis, clinical features, growth parameters, laboratory, radiological, EEG and molecular analysis findings were recorded. The data obtained in the study were analyzed using SPSS 23 (Statistical Package for Social Sciences) software. In statistical analyses, Chi-square analysis and Fisher Exact test were used to examine the relationships between categorical variables. Kruskal-Wallis test and Mann-Whitney U test were used to evaluate the differences between continuous variables since parametric test assumptions were not met. In all analyses, the significance level was determined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and the confidence level was evaluated as 95%. The ethics committee approval of the study was given by the \u0026ldquo;Tekirdağ Dr. İsmail Fehmi Cumalıoğlu City Hospital Clinical Research Ethics Committee\u0026rdquo; on 28.08.2024 with the number 119.\u003c/p\u003e "},{"header":"Findings","content":"\u003cp\u003e\u003cstrong\u003eDemographic Characteristics:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 36 patients with a genetic diagnosis of mitochondrial diseases, 52.8% (n = 19) were female and 47.2% (n = 17) were male. Regarding age distribution, the highest proportion was observed in the 5.01\u0026ndash;10-year age group at 25% (n = 9), whereas the lowest proportion was in the 10.01\u0026ndash;15-year age group at 13.9% (n = 5). The most common period for the onset of initial symptoms was under 5 years of age, accounting for 58.3% (n = 21), while the lowest frequency was recorded in the 15.01\u0026ndash;20-year age group at 2.8% (n = 1). In terms of age at diagnosis, 41.7% (n = 15) of the patients were diagnosed before the age of 5 years, whereas 13.9% (n = 5) were diagnosed after the age of 20 years (Table 1, table 8).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenetic Diagnoses and Distribution by Diagnosis\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eOf the 36 patients with a genetic diagnosis of mitochondrial diseases, 41.7% (n=15) were diagnosed with MELAS, 25% (n=9) with Coenzyme Q10 deficiency, 11.1% (n=4) with Leigh syndrome and 8.3% (n=3) with \u003cem\u003ePOLG\u003c/em\u003e mutation. There were also cases with \u003cem\u003eFBXL\u003c/em\u003e mutation 5.5% (n=2), LHON 2.8% (n=1), Triple H syndrome 2.8% (n=1), and ACAT1 (n=1) 2.8% deficiency (Graph 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStroke-like Attacks:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 14 patients with stroke-like attacks, 42.8% (n=6) were diagnosed with MELAS and 21.4% (n=3) with POLG. These episodes were also observed in individuals diagnosed with Coenzyme Q10 deficiency 14.2% (n=2), Leigh syndrome 14.2% (n=2), and ACAT1 deficiency 7.1% (n=1) (Figure 1). A comparative analysis of the data reveals that the most prevalent age group experiencing stoke-like attacks was 5.01-10 years (42.9%), followed by 15.01-20 years (28.6%). The highest proportion of individuals without an attack was in the age group above 20 years, with 27.3%. However, no statistically significant relationship was found between age groups and stroke-like attacks (\u0026chi;\u0026sup2; = 7.955; p = 0.078) (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Findings Associated with Stroke Attacks\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe prevalence of seizures was found to be significantly higher in patients with a stroke-like episode compared to those without such an episode (64.3% vs. 22.7%, p \u0026lt; 0.05) (p=0.013). Similarly, hemiparesis was observed in 35.7% of patients with a history of attack compared to only 4.8% in those without a history of attack (p=0.028). Psychiatric disorders were also associated with stroke-like attacks; being present in 44.4% of those who had an attack and 9.5% of those who did not (p=0.049). Ophthalmoplegia and hemianopsia were reported only in individuals who had an attack, and both findings were statistically significant (p=0.048) (Graph 2).\u003c/p\u003e\n\u003cp\u003eWhen genetic subtypes were analyzed, migraine headache was reported 100% in \u003cem\u003eFBXL4\u0026nbsp;\u003c/em\u003emutations, ACAT1 deficiency, and Triple H patients, 88.9% in Coenzyme Q10 deficiency, 75% in Leigh syndrome, and 40% in MELAS. Cognitive decline was present in all patients (100%) with Leigh, \u003cem\u003eFBXL4\u003c/em\u003e mutations and LHON. Decreased muscle mass was significantly observed in patients with MELAS, \u003cem\u003eFBXL4\u003c/em\u003e, and Triple H. Cataracts were detected in 50% of individuals with \u003cem\u003ePOLG\u003c/em\u003e mutation only, which was distinctive in this respect. Hearing loss was observed in 50% of patients with \u003cem\u003eFBXL4\u003c/em\u003e mutation (Graph 3). An evaluation of body mass index (BMI) revealed mean BMI values of 16.49\u0026plusmn;3.85 in patients with MELAS, 23.83\u0026plusmn;11.47 in patients with CoQ10 deficiency, 11.98\u0026plusmn;2.97 in Leigh syndrome, and 27.34\u0026plusmn;15.37 in the FBXL, LHON, Triple H, ACAT1 group. Although no significant difference was found between the diagnosis groups (\u0026chi;\u0026sup2; = 7.371; p = 0.061), the p-value is close to the significance limit and suggests that there may be BMI trends according to diagnosis (Graph 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSeizures and EEG findings\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eA history of seizures was identified in 64.3% of stroke patients, while 35.7% had no history of seizures. In the evaluation of seizure types, 35.7% of patients experienced generalized seizures and 28.6% experienced focal seizures. Analysis of EEG findings revealed that EEG evaluation was not performed in 21.4% of the patients, whereas focal epileptiform activity was detected in 35.7%. Additionally, generalized epileptiform activity was observed in 21.4% of patients, while 42.9% showed no evidence of generalized epileptiform activity (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMagnetic Resonance Imaging (MRI) Findings\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eCranial MRI revealed lesions in 51.6% (n=16) of the patients. Of the lesions, 73.3% affected both hemispheres, 20% affected the left hemisphere, and 6.7% affected the right hemisphere. Lesions were most frequently observed in the frontal and temporal lobes (33.3%; n=4), with lower rates in the parietal lobe (24%; n=3) and occipital lobe (8.4%; n=1). Regarding lesion resolution, disappearance occurred within 2\u0026ndash;6 months in 37.5% (n = 3) of patients, between 6 months and 1 year in 12.5% (n = 1), and after more than 1 year in 50% (n = 4) of the patients with available data (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMR Spectroscopy Findings\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eMR spectroscopy was not performed in 52.1% (n=18) of the patients; no lactate peak was found in 25.8% (n=8) and 16.1% (n=5) of the patients who underwent MR spectroscopy (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory Findings\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe mean plasma lactic acid level was 22.61\u0026plusmn;23.24 mg/dL in individuals who had a stroke-like attack, while this value was 10.21\u0026plusmn;12.39 mg/dL in those who did not have an attack. The difference between the two groups was not statistically significant (z=-1.785; p=0.078), but it was close to the significance threshold (Figure 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eDistribution of demographic information and variables related to diagnosis in patients with mitochondrial diseases experiencing stroke-like attacks\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 196px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 196px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e47,2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e52,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 196px;\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u0026lt;5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e19,4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e5.01-10\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e25,0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e10.01-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e13,9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e15.01-20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e22,2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eOver 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e19,4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 196px;\"\u003e\n \u003cp\u003eAge at onset of first symptoms (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u0026lt; 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e58,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e5.01-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e16,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e10.01-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e11,1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e15.01-20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eOver 20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e11,1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 196px;\"\u003e\n \u003cp\u003eAge at diagnosis (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u0026lt;5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e41,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e5.01-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e13,9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e10.01-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e25,0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e15.01-20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eOver 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e13,9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 196px;\"\u003e\n \u003cp\u003eDuration of follow-up (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u0026lt;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e30,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e1.01-2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e16,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e2.01-3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e16,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e3.01-4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e13,9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003e\u0026gt;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e22,2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" style=\"width: 196px;\"\u003e\n \u003cp\u003eDiagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e41,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eCoenzyme Q10 deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e25,0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eLeigh syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e11,1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003ePOLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e8,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eFBXL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e5,5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eLHON\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eTriple H syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 190px;\"\u003e\n \u003cp\u003eACAT1 deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 107px;\"\u003e\n \u003cp\u003e2,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, LHON: Leber\u0026apos;s hereditary optic neuropathy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u0026nbsp;\u003c/strong\u003eCranial MR findings of the patients\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"509\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 379px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 65px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 230px;\"\u003e\n \u003cp\u003eCranial MRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eLesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e51,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e48,4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 230px;\"\u003e\n \u003cp\u003eLocalization Lesions 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eRight hemisphere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e6,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eLeft hemisphere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eBilateral hemispheres\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e73,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 230px;\"\u003e\n \u003cp\u003eLocalization Lesions 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e33,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e33,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eParietal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eOccipital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e8,4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 230px;\"\u003e\n \u003cp\u003eTime to Resolution of Lesions (Month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026nbsp;2-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e37,5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e6-12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e12,5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003e\u0026gt;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 230px;\"\u003e\n \u003cp\u003eMR Spectroscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eNot performed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e58,1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eLactate peak detected\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e16,1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 148px;\"\u003e\n \u003cp\u003eNo lactate peak\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e25,8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003en: frequency, %: percentage\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3:\u0026nbsp;\u003c/strong\u003eDistribution of stroke patients (n=14) regarding diagnosis and seizures\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"484\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 372px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 145px;\"\u003e\n \u003cp\u003eSeizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e64,3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 145px;\"\u003e\n \u003cp\u003eSeizure Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eFocal seizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e28,6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eGeneralized seizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo information\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 145px;\"\u003e\n \u003cp\u003eEEG Finding 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo EEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e28,5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eFocal epileptiform activity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo focal epileptiform activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 145px;\"\u003e\n \u003cp\u003eEEG Finding 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eGeneralized epileptiform activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e21,4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo generalized epileptiform activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e42,9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eNo EEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e35,7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 145px;\"\u003e\n \u003cp\u003eEEG Finding 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eEpileptiform activity in the left frontotemporal region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eEpileptiform activity in the temporaparietal region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003eEpileptiform activity in the left hemisphere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4:\u0026nbsp;\u003c/strong\u003eAge and stroke attack findings\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"537\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" rowspan=\"2\" valign=\"bottom\" style=\"width: 217px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStroke-like Attacks\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"10\" style=\"width: 64px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026lt;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"12\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7,955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"12\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0,078\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e21,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e18,2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e19,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e5.01-10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e42,9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e13,6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e25,0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e10.01-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e0,0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e22,7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e13,9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e15.01-20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e28,6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e18,2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e22,2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026gt;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e7,1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e27,3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e19,4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 153px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e100,0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e100,0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e100,0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe graph shows the incidence of stroke-like attacks in individuals with different diagnostic groups. It is noteworthy that stroke-like attacks are more common in individuals with MELAS and POLG mutations. There is one patient diagnosed with ACAT1 and had a stroke attack.\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003cbr\u003e\u0026nbsp;In the graph, the red line indicates the significance limit (p=0.05).\u003c/p\u003e\n\u003cp\u003eThe heat map above shows the percentages of certain neurological and systemic symptoms by diagnosis. The color intensity is darker the more common the symptom is in that diagnostic group\u003c/p\u003e\n\u003cp\u003eThe graph shows the mean and standard deviation of body mass index (BMI) of individuals belonging to different diagnostic groups. The \u0026apos;mean \u0026plusmn; standard deviation\u0026apos; values for each diagnostic group are also indicated on the graph.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe graph shows the mean and standard deviation values of lactic acid levels in individuals with and without stroke-like episodes. Lactic acid levels were higher and the distribution was wider in individuals with stroke. This difference was statistically borderline significant (p=0.078).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 8\u003c/strong\u003e: Clinical findings of the patients\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMutation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at onset of first symptoms\u003c/strong\u003e \u003cstrong\u003e(months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis (months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of stroke-like episodes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLocalization of lesions on cranial MRI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEEG\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003efindings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLactate levels mmol/L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(last viewed)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of oral L-Arginine use\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TK\u003c/em\u003e-M8362T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e2 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A3243G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eFrontal deceleration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e22 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e16,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A323G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TK\u003c/em\u003e-M3290T\u0026gt;C\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eParietal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eEpileptiform activity in the left fronto-temporal region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A3243G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e22 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TW\u003c/em\u003e- 5543T\u0026gt;C\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e11,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TK\u003c/em\u003e-M8362T\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-Nt3243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eParietal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eEpileptiform activity in the left fronto-temporal region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TW-\u003c/em\u003e5543T\u0026gt;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e3,7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-m3243A\u0026gt;G\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eTemporo parietal bilateral epileptiform activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e9 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TL1\u0026nbsp;\u003c/em\u003em3271T\u0026gt;C\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eOccipital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eLow background activity and rare spike-like waves in the right parieto-occipital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e11 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e15,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A3243G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eLeft hemisphere epileptiform activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e40 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e5,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A323G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e11 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e18,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eTRLN1\u003c/em\u003e-A323G\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eMELAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-TL1\u0026nbsp;\u003c/em\u003em3271T\u0026gt;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eParietal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e34 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e21,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8A\u0026nbsp;\u003c/em\u003ec.911C\u0026gt;T hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eDisorganization in the left fronto-temporal region\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e4,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ4\u0026nbsp;\u003c/em\u003ec.437T\u0026gt;G\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e2,5\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e17,8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8\u0026nbsp;\u003c/em\u003ec.811C\u0026gt;T (p.ARG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eMultifocal generalized epileptiform anomaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e19,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8A\u0026nbsp;\u003c/em\u003ec.914A\u0026gt;T hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eFrontal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e1day\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e22,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8B\u0026nbsp;\u003c/em\u003ehom. c1199dup\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;COQ8A\u003c/em\u003e c.811 C\u0026gt;T (p.ARG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eMultifocal generalized epileptiform anomaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e6,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8A\u0026nbsp;\u003c/em\u003ec.1344_1345dup hom.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1,49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e6,00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;COQ4\u0026nbsp;\u003c/em\u003ec.437T\u0026gt;G (p.Phe146C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e10,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eCoenzyme Q10 Deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eCOQ8\u0026nbsp;\u003c/em\u003ec.811C\u0026gt;T 9(p.ARG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3,40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e2,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eLeigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eLINS gen\u0026nbsp;\u003c/em\u003ec.554a\u0026gt;G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e1,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eLeigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eSURF1\u0026nbsp;\u003c/em\u003ec.530T\u0026gt;G hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e3 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e6,9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eLeigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eMT-ND5\u0026nbsp;\u003c/em\u003eM.13513G\u0026gt;A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eLeigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eSURF1 gene\u0026nbsp;\u003c/em\u003ec54+5G\u0026gt;T (IVS1+5G\u0026gt;T) hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e1,4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003ePOLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003ec.3286C\u0026gt;T p.Arg1096h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eBilateral central disorganization in sleep\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e7,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003ePOLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003ec.1760C\u0026gt;T P. Pro587leu */c1760C\u0026gt;T.pro587leu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e9,1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003ePOLG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003ec.911T\u0026gt;G\u0026nbsp;\u003c/em\u003e(p. Leu304Arg) hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e12,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eFBXL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eFBXL4\u0026nbsp;\u003c/em\u003ec.445G\u0026gt;A\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eFBXL4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eFBXL4\u0026nbsp;\u003c/em\u003ec.445G\u0026gt;A\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e10,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e18,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eLHON\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eLHON\u0026nbsp;\u003c/em\u003e11778G\u0026gt;A\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eTriple-H syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eSLC25A15\u0026nbsp;\u003c/em\u003ehom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e120 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 5px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 5px;\"\u003e\n \u003cp\u003e5,5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003eACAT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cem\u003eACAT1\u0026nbsp;\u003c/em\u003ec.301C\u0026gt;T hom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003eNo lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2,2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this multicenter observational cohort study, the clinical, radiological, EEG, and genetic features of genetically diagnosed mitochondrial diseases, the frequency of stroke-like episodes, associated findings, and treatment approaches were evaluated. Although the data obtained were generally consistent with the existing literature, they also showed some remarkable differences.\u003c/p\u003e \u003cp\u003eStroke-like attacks were most frequently observed in individuals diagnosed with MELAS (42.9%), as reported in the literature (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In the majority of these patients (66.6%), m.3243A\u0026thinsp;\u0026gt;\u0026thinsp;G mutation was found in the \u003cem\u003eMT-TL1\u003c/em\u003e gene, and this rate was consistent with previously reported data (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). \u003cem\u003ePOLG\u003c/em\u003e mutation stood out as the second most common cause of stroke-like attacks, and this was consistent with the frequency ranking in the literature (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCoenzyme Q10 (CoQ10) deficiency is one of the rare mitochondrial disorders that develop due to mutations in genes involved in ubiquinone synthesis. In the literature, there are a limited number of cases and small patient series in which stroke-like attacks have been reported to be associated with mutations in biosynthesis genes such as COQ8A (ADCK3) and COQ4 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our study, stroke-like attacks were observed in two of nine patients diagnosed with CoQ10 deficiency. This finding indicates that CoQ10 deficiency may rarely lead to stroke-like attacks and emphasizes that neurologic symptoms should be carefully evaluated in this patient group.\u003c/p\u003e \u003cp\u003eIn beta-ketothiolase deficiency due to \u003cem\u003eACAT1\u003c/em\u003e mutation, basal ganglia involvement, and neurologic findings may be observed during ketoacidosis attacks that develop after metabolic stress. In the literature, a case of stroke-like episode with ketoacidosis after infection has been reported (17). In our study, a stroke-like episode was observed during the metabolic crisis in a patient with \u003cem\u003eACAT1\u003c/em\u003e mutation. This finding demonstrates that \u003cem\u003eACAT1\u003c/em\u003e-related metabolic diseases may present not only with metabolic crises but also with acute neurologic complications. It is therefore suggested that stroke-like episodes should definitely be considered in the differential diagnosis in this patient group.\u003c/p\u003e \u003cp\u003eStroke-like episodes associated with Leigh syndrome have rarely been described in the literature. In a case report, a three-month-old female infant with post-infectious encephalopathic features and neurologic symptoms, including hypotonia, apnea, and optic atrophy was diagnosed with Leigh syndrome. This case suggests that metabolic stress may trigger neurologic findings in Leigh syndrome, and the disease may present with stroke-like episodes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In our series, it was observed that two of the four patients with Leigh syndrome developed stroke-like episodes in relation to metabolic stress. This observation reveals that Leigh syndrome may present not only as a progressive neurodegenerative disorder but also with acute neurologic decompensations triggered by metabolic stress. It emphasizes the necessity for early diagnosis, close follow-up, and prevention of metabolic crises in this patient group.\u003c/p\u003e \u003cp\u003eIn a study conducted by Chloe Durrleman et al. on 120 pediatric patients, it was reported that the first symptoms of the patients started between 0\u0026ndash;28 months, and the first stroke-like attacks occurred between 17\u0026ndash;124 months. In addition, it was reported that 32% of the patients had their first stroke-like attack over the age of 35 years in this series (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In our study, it was observed that the first symptoms usually started before the age of 5 years, and the first stroke-like attacks occurred mostly in the age range of 5.01-10 years (42.9%). The youngest patient was 1.9 years old, and the oldest patient was 40 years old. This shows that the development of attacks is not limited by age and can occur at any age. Gender distribution was equal (F/M: 7/7), and gender was not a determining factor in attacks. In this respect, it differs from some studies in the literature (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e). An analysis of the clinical symptoms revealed that headache was the most prevalent indication associated with stroke-like attacks. This was followed by decreased muscle mass, myopathy, and seizures. In a study by Chaolong Xu et al. involving children with MELAS syndrome, muscle weakness was defined as an indicator of severe mitochondrial dysfunction (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e). The high seizure frequency found in our study and its significant association with stroke-like episodes support the hypothesis that these episodes may be triggered by epileptic seizures (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn a study conducted by Yi Shiau Ng et al. on MELAS patients, it was reported that 91% of the patients had symptoms indicating mitochondrial dysfunction before the stroke-like attack, and the most common symptom was sensorineural hearing loss (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In our series, findings such as hearing loss, hemianopsia, cortical blindness, recurrent vomiting, and myopathy were frequently observed before stroke-like attacks in individuals diagnosed with MELAS. In addition, sensorineural hearing loss was one of the most common symptoms in these patients. Although no statistical significance was found between stroke-like attacks and some demographic variables such as age, gender, and BMI, low BMI in MELAS and Leigh patients is remarkable. This indicates that short stature and nutritional deficiency also accompany these patients and is in parallel with the literature (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eStudies have shown that brain lactate levels increase with disease progression in MELAS patients, and this increase reflects a progressive shift in oxidative redox potential. These findings suggest that lactate levels may be an important biomarker for monitoring the course of the disease and establishing a diagnosis. In our study, mean lactate levels were found to be significantly higher in patients with a stroke-like attack compared to those without an attack (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e22\u003c/span\u003e). This difference was close to the statistical significance limit and may support the potential role of lactic acidosis in the pathogenesis of the attack. Therefore, regular monitoring of lactate levels may be useful in clinical follow-up.\u003c/p\u003e \u003cp\u003eIn radiologic evaluations, Durrleman et al. reported that bilateral cortical diffusion hyperintensity and hyperperfusion were prominent in cranial MR images obtained in the first 48 hours, and this condition developed due to energy metabolism disorders different from classical ischemic strokes (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e21\u003c/span\u003e). In our study, bilateral lesions were observed in all seven patients imaged in the acute period, and the most common site of involvement was frontotemporal lobes. When EEG findings were analyzed, focal epileptiform activity was found to be more frequent in accordance with the literature (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWith regard to the treatment approaches that were employed, a retrospective analysis by Ganetzky et al. reported that clinical improvement was achieved in 47% of patients who received intravenous (iv) arginine treatment. A better response to treatment was observed, especially in cases of hemiplegic attacks (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In our series, all patients with stroke-like attacks received iv arginine treatment in the acute phase of the attack, and clinical improvement was observed, especially in the early onset case in Durrleman's study, recurrent attacks were reported in three patients in an 8-year follow-up, whereas recurrent stroke-like attacks were observed in six patients in our series, with five attacks in one MELAS patient and four attacks in another (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn systematic reviews on the efficacy of oral L-arginine treatment, it was emphasized that the clinical benefit of acute or prophylactic use was limited, but methodological deficiencies were found in these studies (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e24\u003c/span\u003e). On the other hand, some studies have suggested that oral L-arginine may reduce the frequency and severity of stroke-like episodes. In a study including six MELAS patients, it was reported that oral L-arginine treatment at a dose of 0.15\u0026ndash;0.3 g/kg/day administered for 18 months resulted in significant improvement (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In our study, long-term oral L-arginine treatment was administered to 10 MELAS patients with recurrent stroke-like attacks, and significant improvement was observed in the clinical course. In addition, Chaolong Xu et al. reported that 56% of patients receiving L-arginine and antiepileptic treatment showed significant clinical improvement (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study showed that stroke-like attacks in genetically diagnosed mitochondrial diseases are most commonly observed in MELAS and \u003cem\u003ePOLG\u003c/em\u003e mutations. However, they may also develop in rare subtypes such as CoQ10 deficiency, \u003cem\u003eACAT1\u003c/em\u003e mutation, and Leigh syndrome. During attacks, the presence of bilateral cortical lesions on cranial MRI\u0026mdash;often located in the frontotemporal regions and inconsistent with vascular distribution\u0026mdash;and the detection of focal epileptiform activity on EEG were diagnostically significant findings. Clinical improvement was observed with iv L-arginine treatment initiated in the acute period, and it was determined that long-term oral arginine may be effective in reducing the frequency of attacks. The findings emphasize that stroke-like episodes should be considered in the differential diagnosis of mitochondrial diseases in cases of sudden onset neurological findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: This research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e All authors contributed to the study conception and design\u003cem\u003e.\u0026nbsp;\u003c/em\u003eAll authors have accepted responsibility for the entire content of this manuscript and approved its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e Authors state no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e: Informed consent was obtained from all individuals included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAho K, Harmsen P, Hatano S, Marquardsen J, Smirnov at all. 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Mitochondrial en cephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci. 2008;1142:133-58.\u003c/li\u003e\n\u003cli\u003eKoga Y, Akita Y, junko N, Yatsuga S, Povalko N, et all. Endothelial dysfunction in MELAS improved by l-arginine supplementation. Neurology. 2006;66:1766-9.\u003c/li\u003e\n\u003cli\u003eXu C, Dai S, Jiang H, Liu Z, at all. Clinical characteristics and long-term prognosis of 150 children with MELAS syndrome in China. J Neurol. 2025 Mar 21;272(4):280. doi: 10.1007/s00415-025-13009-z.\u003c/li\u003e\n\u003cli\u003eNg YS, Lax NZ, Blain AP, Erskine D, Baker MR, at all. Forecasting stroke-like episodes and outcomes in mitochondrial disease. Brain. 2022 Apr 18;145(2):542-554. doi: 10.1093/brain/awab353. \u003c/li\u003e\n\u003cli\u003eRamesh R, Hariharan S, Sundar L. Stroke-Like Episodes and Epilepsy in a Patient with COQ8A-Related Coenzyme Q10 Deficiency. Ann Indian Acad Neurol. 2023 Nov-Dec;26(6):980-982. doi: 10.4103/aian.aian_511_23.\u003c/li\u003e\n\u003cli\u003eBosch AM, Kamsteeg EJ, Rodenburg RJ, van Deutekom AW, Buis DR at all. Coenzyme Q10 deficiency due to a COQ4 gene defect causes childhood-onset spinocerebellar ataxia and stroke-like episodes. Mol Genet Metab Rep. 2018 Sep 13;17:19-21. doi: 10.1016/j.ymgmr.2018.09.002. \u003c/li\u003e\n\u003cli\u003eRostami P, Mohsenipour R, Kameli R, Garshasbi M, Ashrafi MR, at all. Beta-Ketothiolase Deficiency as A Treatable Neurometabolic Disorder: A Case Report Due to A Novel Compound Heterozygote Mutations in ACAT1 Gene. \u003cem\u003eBiomed J Sci Tech Res.\u003c/em\u003e 2019;15(4):1\u0026ndash;4. doi:10.26717/BJSTR.2019.15.002697.\u003c/li\u003e\n\u003cli\u003eHaliloğlu B, Fedakar A. 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Long-term prognostic factors and outcomes in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes: a clinical and biochemical marker analysis. Front Neurol. 2024 Dec 4;15:1491283. doi: 10.3389/fneur.2024.1491283.\u003c/li\u003e\n\u003cli\u003eGanetzky RD, Falk MJ. 8-year retrospective analysis of intravenous arginine therapy for acute metabolic strokes in pediatric mitochondrial disease. Mol Genet Metab. 2018 Mar;123(3):301-308. doi: 10.1016/j.ymgme.2018.01.010. \u003c/li\u003e\n\u003cli\u003eStefanetti RJ, Ng YS, Errington L, Blain AP, McFarland R, at all. l-Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes: A Systematic Review. Neurology. 2022 Jun 7;98(23):e2318-e2328. doi: 10.1212/WNL.0000000000200299.\u003c/li\u003e\n\u003cli\u003eAlmannai M, El-Hattab AW. Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline. Front Mol Neurosci. 2021 Aug 5;14:682780. doi: 10.3389/fnmol.2021.682780. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Stroke-like episodes, mitochondrial diseases. MELAS, POLG mutations, CoQ10 deficiency","lastPublishedDoi":"10.21203/rs.3.rs-6950590/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6950590/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eIntroduction\u003c/b\u003e: Stroke-like attacks are defined as events characterized by the sudden onset of neurological symptoms with clinical manifestations similar to those of a stroke. However, they are distinguished by the presence of radiological lesions that are incompatible with the vascular territory. MELAS syndrome, which is characterized by metabolic encephalopathy, lactic acidosis, and stroke-like attacks, has been identified as the first genetically defined and most widely known mitochondrial cause of stroke-like attacks. It has been demonstrated that stroke-like attacks may occur in the course of a variety of mitochondrial diseases, including those that are the result of nuclear DNA mutations.\u003c/p\u003e \u003cp\u003e \u003cb\u003eObjective\u003c/b\u003e: In this retrospective, multicenter, observational cohort study, we sought to determine the clinical, radiological, EEG, and genetic characteristics of patients with mitochondrial gene mutations presenting with stroke-like attacks and the frequency and treatment of stroke-like attacks.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e: Thirty-six patients with mitochondrial disease with stroke-like episodes, all diagnosed by molecular analysis from nine pediatric metabolic disease centers in the Marmara Region of Turkey, were included in the study. Demographic characteristics, symptoms, clinical features, cranial MRI, EEG findings, and genetic characteristics were evaluated.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusion\u003c/b\u003e: The present study demonstrated that stroke-like attacks in genetically diagnosed mitochondrial diseases are most commonly observed in MELAS and POLG mutations. However, they may also develop in rare subtypes such as CoQ10 deficiency, beta-ketothiolase deficiency (\u003cem\u003eACAT1\u003c/em\u003e mutation), and Leigh syndrome.\u003c/p\u003e \u003cp\u003eDuring attacks, cranial MRI showed bilateral cortical lesions incompatible with vascular distribution, often located frontotemporally, and EEG shows focal epileptiform activity. In MELAS, clinical improvement was observed withiv L-arginine treatment initiated in the acute period, and it was determined that long-tMEerm oral arginine may be effective in reducing the frequency of attacks. The findings emphasize that stroke-like episodes should be considered in the differential diagnosis of mitochondrial diseases in the presence of sudden onset neurological findings.\u003c/p\u003e","manuscriptTitle":"How to interpret stroke-like attacks in the context of mitochondrial disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 07:24:20","doi":"10.21203/rs.3.rs-6950590/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0a298a8e-1887-4f28-888e-4e178bc5eb72","owner":[],"postedDate":"June 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-29T06:38:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-25 07:24:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6950590","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6950590","identity":"rs-6950590","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}